Enhancement of Esterification Reaction Rates in Solvent-Free Aerosol Droplets

Aerosols are appealing vessels for accelerating chemical reactions owing to their high surface area-to-volume ratios and capacity to access supersaturated solute states. Although many studies demonstrate enhanced reaction rates in charged droplets using electrospray ionization-mass spectrometry, such studies have poor control over experimental parameters including droplet size, water content, and imparted charge and generally cannot explore the reaction’s reversibility. Here, an esterification reaction between a dicarboxylic acid and low-volatility alcohol (that in bulk synthesis requires reflux at 160 °C for ∼15 h in nonaqueous solvent) is investigated in aqueous aerosol droplets spanning picoliter to sub-femtoliter volumes. Individual picoliter droplets generated without applied external voltage were confined within an Aerosol Optical Tweezers instrument, and Raman spectroscopy was used to resolve chemical change in the droplets. Flow tube experiments on sub-femtoliter aerosol droplets were conducted using both online aerosol mass spectrometry and off-line NMR spectroscopy. Across both droplet volume scales, the esterification was facile (<400 s in picoliter droplets, <2 s in sub-femtoliter droplets) upon droplet dehydration at room temperature. We demonstrate that both the forward and reverse reaction are vastly accelerated in aerosol compared to macroscopic solution. The unique aspects of this study include rigorous control over a water activity range spanning dilute to solvent-free conditions, investigation across a broad droplet volume range, application of multiple analytical techniques to confirm independently accelerated reactivity, and exploration of the reaction’s reversibility. Combined, this study demonstrates how aerosols can drive chemistry in accordance with Le Chatelier’s principle on both the micro- and nanoscales.